To determine the concentration of theophylline or caffeine in the blood to establish an appropriate dose and to maintain a therapeutic level

When To Get Tested?

At the start of drug therapy and at regular intervals to monitor the drug's concentration; when indicated, to detect low or excessive (potentially toxic) concentrations

Sample Required?

A blood sample drawn from a vein in your arm or from pricking an infant's heel

Test Preparation Needed?

None

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Theophylline and caffeine are drugs that ease breathing and stimulate respiration (methylxanthines). These tests measure the amount of theophylline or caffeine in the blood to help establish an appropriate dose and to maintain a therapeutic level.

Theophylline is one of several medications that may be taken by children and adults who have asthma and by adults who have chronic obstructive pulmonary disease (COPD). It is a bronchodilator with a narrow therapeutic window – too little theophylline is ineffective, too much can cause toxicity. Both short-acting and long-acting formulations are available for asthma treatments. Acute theophylline toxicity presents with rapid heart rate and nausea. Chronic theophylline toxicity is associated with an increased risk of seizures and abnormal heart rhythms (cardiac dysrhythmias). Both acute and chronic toxicity can be life-threatening.

Caffeine is frequently used for adults as a pain reliever (analgesic), migraine remedies, and to remain alert and/or awake. It is also the preferred medication to treat apnea in premature newborns. Apnea compromises the amount of oxygen available to the body. It is a common and serious condition in premature newborns that must be promptly treated and closely monitored. While both medications can reduce episodes of apnea, caffeine has fewer side effects than theophylline and, thus, a lower risk of toxicity. At very high doses, symptoms similar to those found with theophylline toxicity may be seen.

Establishing and maintaining therapeutic doses can be a challenge. Both theophylline and caffeine levels may need to be monitored because the range of concentrations in which the drugs are effective but not toxic is narrow and in some cases the dose given does not always correlate well with concentrations in the blood.

The rate at which the drugs are metabolized will vary from person to person; it is decreased in both the very young and the elderly and increased in smokers. The drug levels may also be affected by underlying conditions such as pneumonia, liver disease, hypothyroidism, and by acute infection or illness. Many drugs interact and interfere with the metabolism of theophylline and caffeine. They may increase or decrease its rate of metabolism.

How is the sample collected for testing?

A blood sample is obtained by inserting a needle into a vein in the arm. In infants, blood may be collected by pricking a heel.

Is any test preparation needed to ensure the quality of the sample?

Theophylline and caffeine tests are used to monitor the amount of the drugs in the blood to establish appropriate doses and to maintain therapeutic levels. Theophylline and caffeine are used to ease breathing and stimulate respiration.

Theophylline is usually ordered as a trough level – prior to the next dose when the concentration is expected to be at its lowest level. Tests may also be ordered if a health practitioner suspects that a person may be experiencing theophylline toxicity. A series of blood samples may be collected and tested over a period of time to track theophylline concentrations in someone who has had high theophylline levels, until therapeutic concentrations are reached.

Caffeine blood levels are not used to monitor therapy as routinely as theophylline tests. Usually, newborns receiving caffeine are monitored clinically for episodes of apnea and signs of toxicity, and physiological effects of the drug are closely watched. The majority of those treated respond to standardized doses of the medication without the need for monitoring blood caffeine levels. The test is primarily ordered if an infant is not responding to therapy as expected or if the infant is demonstrating signs of toxicity. Since daily doses and an extended half-life in the premature neonate generally result in stable drug levels, the sample collected is usually a random level, not a trough level.

When a person is beginning theophylline treatment, the theophylline test may be ordered several times as the dosage is adjusted as needed, until therapeutic levels are attained. The test may be ordered whenever a person has symptoms that the health practitioner suspects are due to theophylline toxicity and whenever a person is not responding as expected to therapy. A healthcare provider may order multiple theophylline tests when someone is being treated for theophylline toxicity. The health practitioner may order a test when a person taking theophylline experiences a significant change in health status and/or when the person starts or discontinues taking a drug that is known to affect the metabolism of theophylline.

A caffeine test may be ordered whenever a premature neonate is not responding as expected to treatment and/or whenever an infant has symptoms that the health practitioner suspects are related to high caffeine levels. Signs and symptoms associated with high caffeine levels in a newborn may include:

The therapeutic concentration for theophylline, when used as a bronchodilator to treat asthma, is generally considered to be 5–15 mcg/mL (28-83 micromol/L) for adults, 5–10 mcg/mL (28–55 micromol/L) for children and neonates. Levels greater than 20 mcg/mL (111 micromol/L) are considered toxic. Some people may experience significant side effects at concentrations less than 20 mcg/mL (111 micromol/L). When theophylline is used to treat apnea in premature neonates, the therapeutic range is 6-11 mcg/mL (33-61 micromol/L).

Therapeutic concentration for caffeine for the treatment of premature neonate apnea is much wider, 5-20 mcg/mL (25-103 micromol/L), while concentrations greater than 20 mcg/mL (103 micromol/L) are considered toxic, and greater than 50 mcg/mL (257 micromol/L) are considered critical values.

Low levels of theophylline and caffeine may indicate that the drug has not reached a therapeutic level for the individual tested and there is insufficient drug present to be effective.

Blood levels in the therapeutic range mean that most people will have their symptoms relieved without experiencing significant side effects. Adverse side effects and the risk of seizures increase with higher concentrations of these drugs.

Theophylline can affect, and be affected by, a wide variety of drugs and compounds. When a health practitioner prescribes theophylline, it is important for a person to list and discuss all of the prescribed and over-the-counter medications that they are taking, including oral contraceptives and any herbal supplements such as echinacea, chamomile, and gingko. The healthcare provider will also want to know the amount of caffeine and alcohol that a person is consuming and whether or not the person smokes.

The use of theophylline as a bronchodilator has decreased as other more effective and less toxic asthma treatments have become available. It is still in use throughout the United States but is not generally the first treatment choice.

In infants, a significant amount of the theophylline dose (8.5%) is metabolized to caffeine. This occurs to a much lesser degree in children and adults. In cases where the theophylline concentration is within the therapeutic range but the infant is showing signs of toxicity, caffeine levels should be determined. Likewise, theophylline is one of the metabolites of caffeine.

Ram, F. (2006 March 8). Use of Theophylline in Chronic Obstructive Pulmonary Disease: Examining the Evidence. Medscape From Current Opinion in Pulmonary Medicine [On-line information]. Available online at http://www.medscape.com/viewarticle/524508 through http://www.medscape.com. Accessed on 9/14/08.

(2011 February 1). How Is Asthma Treated and Controlled? National Heart Lung and Blood Institute [On-line information]. Available online at http://www.nhlbi.nih.gov/health/health-topics/topics/asthma/treatment.html through http://www.nhlbi.nih.gov. Accessed February 2012.

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